Last year, we identified two novel variants of histone 2A using two dimensional gel analysis. This year, we have developed a sensitive and quantitative peptide mapping technique and have proceeded with the characterization of these variants. We have found these two histones, called H2A.X and H2A.Z, in sea urchins as well as in human and mouse cell lines, a finding which suggests that these two proteins may be universal chromosome components. We have developed methods for quantitating the modification of histone using peptide analysis and have compared the modification patterns of H2A's. The H2A.Z variant is particularly interesting because it is not modified in the same way as other H2A's. Last year we reported also the identification of ubiquitin adducts of all the H2A's. This year we report the identification of a uniquitin adduct of H2B. Also we have found that the ubiquitin moiety of the uH2A's turns over independently from the H2A moiety. Studies of the effects of drugs on the metabolism of the nuclear proteins are in progress.